Chinas 100,000-person genome project will be completed in four years, once called off

 Chinas 100,000-person genome project will be completed in four years, once called off

Who am I? Where am I from? Where am I going? This ultimate philosophical proposition has many different perspectives. The answer given from a genetic point of view is undoubtedly a very important one.

In recent years, news in the field of gene has turned the professional topics of gene detection, gene editing, cancer targeting therapy, which originally belong to the field of biomedicine, into a public topic.

Peoples curiosity about genes is: how do genes affect human appearance, height, IQ and health? Can genetic modification free humans from cancer, AIDS, blindness and other diseases? Will superhumans emerge through genetic modification? What problems can genetic testing solve? Why do people oppose gene editing? What are the consequences of the leakage of genetic information?

The reporter of China Economic Weekly interviewed many top experts and scholars in the industry, hoping to unveil the mystery of gene.

What secrets are hidden in genes?

It takes at least 265 to 350 genes to make up a simple life. People are made up of more than 20,000 genes. They have different gene codes. Everyones genes are different.

Gene is an important factor affecting peoples appearance, height and IQ. Some people eat nothing fat, others eat everything fat, which is caused by genes.

So what secrets are hidden in genes?

Why are Southerners more immune than Northerners

Yang Hui, a researcher at the Institute of Neuroscience of the Chinese Academy of Sciences, told China Economic Weekly that the DNA sequence of each gene in human beings is slightly different. Such differences lead to differences in gene expression. Trace changes combined with polygenic combinations will lead to different characteristics, For example, sometimes single gene changes, such as blood type, single eyelid or double eyelid, etc. Polygenic changes, such as skin color, height, weight, personality, hair color, etc.

On October 10, Huada Genome released the data of Chinese genomics, which showed that environmental factors such as diet, climate and pathogens affect Chinese genes in different latitudes, and the differences between southern and northern people are closely related to this.

Because it was difficult to obtain vegetables in ancient northern and northwestern areas, people living in these areas had a large proportion of meat intake, and the alleles promoting fat metabolism had a clear trend of enrichment in these areas; while ancient southern China was called Nanmangyang, where the natural environment was bad, pathogenic microorganisms, especially malaria, were prevalent, and southern people were related to the immune function of the organism. The gene CR1 encoding erythrocyte complement receptor I is enriched.

That is to say, due to the environmental impact of genes, northern people have faster fat metabolism, while southern people have stronger immunity.

Genes have a greater impact on human health. In terms of disease, single genes can lead to hemophilia and thalassemia, while cancer has genetic factors, but most of them are caused by adult (i.e., acquired) cell mutations, Yang Hui said.

It has been reported that scientists at the University of Cambridge in the United Kingdom have confirmed through experiments that alcohol can damage the DNA of hematopoietic stem cells, thereby changing the order of DNA and increasing the risk of cancer.

However, Yang Hui believes that it is difficult to predict the association between alcohol and cancer risk. Its hard to say whether alcohol experiments in mice are the same as in humans.

Hawking warns: Superhuman or destroy ordinary people

Recently, a report from Imperial College of Technology triggered a heated debate in the industry, with researchers identifying for the first time two specific clusters of genes in the human brain associated with IQ.

Does this mean that we can make ourselves smarter by changing our genes?

According to Yang Huis analysis, it is possible to change human defects and make people choose appearance and intelligence quotient, but the technology is not mature enough to solve the problem of chimera (some cells have changed successfully, some cells have not changed), and it is easy to miss the target (originally intended to change A gene, and finally changed B gene).

We dont know enough about life, about these sequences, about which genes really improve IQ. Even the most basic is not clear, how to make it better? Yang Hui said.

It is noteworthy that the late British scientist Stephen Hawking expressed concern about the use of genetic modification of human beings. In Hawkings last book, A Short Answer to Serious Questions, it is mentioned that there may be a superhuman with DNA mutation in the future. This superhuman has a longer life span, intelligence and immunity than ordinary people.

In his book, Hawking argues that once rich people have the opportunity to alter the DNA of their offspring, there will be a new race competition. The children of the upper class will become a new race with more intelligence, longevity and immunity, while the living space of the ordinary people will be squeezed, even destroyed by the new race.

Yang Hui commented on this: It is possible, but this kind offutureis still early. On the one hand, at the technical level, on the other hand, we do not know enough about biology. In the next 10 years, it will be possible to change the genetic traits of a single gene, but many genetic traits are caused by multiple genes, which is very difficult to do.

Although it will take a long time to optimize humans by altering their genes, Hawkings warning has sparked heated debate for a long time.

One view holds that if Hawkings prediction becomes reality, the people with genetic defects will gradually disappear, and the survival of the population with perfect genes is the inevitable choice for survival of the fittest and evolution of species; while another view holds that survival of the fittest is justifiable, but if the number of assets becomes the basis for survival of the fittest, it will be contrary to fairness and ethics. Morality.

Overview of Shenzhen National Gene Bank (Visual China)

Chinas 100,000 Genome Project will be completed in four years

In order to explore the true mystery of genes, the Human Genome Project was born.

The Human Genome Project (HGP), together with the Manhattan Project and the Apollo Project, is known as the Lunar Landing Project of life science.

In 1990, the United States Department of Energy and the National Institutes of Health jointly launched the Human Genome Project. Britain, Japan, France, Germany and other countries have joined in.

From 1998 to 1999, China established the National Centre for the Study of the South of the Human Genome in Shanghai and the North Research Center in Beijing. In July 1999, China actively participated in the International Human Genome Register. It undertook 1% of the tasks and became the only developing country to participate in the project.

On April 15, 2003, the Human Genome Project was completed.

Yang Hui, a researcher at the Institute of Neuroscience, Chinese Academy of Sciences, told China Economic Weekly that the Human Genome Project is to map out all human DNA, with 3 billion base pairs. Every country is responsible for a point and eventually splices it together. Although China only participates in 1% of the work of the Human Genome Project, it is of great significance that China has not lost the opportunity for the development of the biological industry.

Take thalassemia as an example. In the past, when we went to the doctors office, doctors would say that it was characterized as thalassemia. But if we really want to make a diagnosis, we need to know whether the DNA sequence has changed. The human gene pool is a reference for comparing normal human genes with diseases such as thalassemia. With a database, you can tell the patient exactly which sequence of lesions has occurred. Yang Hui said.

On November 28, 2017, China launched the China 100,000 Genome Project, which is the first major national project in the field of human genome research in China and the largest human genome project in the world.

It is reported that the China 100,000 Genome Project will eventually complete the 100,000-scale Chinese genome map and Chinese health map.

Once the genome mapping is completed, the code of 25,000 genes in Chinese human body will be completely decoded, and the relationship between disease health and genetic inheritance in Chinese people will be at a glance.

To the delight of life science researchers, Chinas project is the fastest-moving genome project in the world and will be completed in four years.

Research on assistant gene editing of cloned monkeys in China?

Thanks to the efforts of domestic researchers, China has made rapid progress in gene research. In some areas, such as cloning technology, it has even achieved overtaking in bends.

Since the birth of Dolly, the first cloned sheep in 1996, scientists have cloned cattle, mice, cats, dogs and other animals using somatic cells for more than 20 years, but they have not solved the problem of cloning non-human primates, which is the closest to human beings. Previously, scientists generally believed that the existing technology could not clone primates.

Sun Qiangs team of the Institute of Neuroscience of the Chinese Academy of Sciences has successfully broken through this difficult problem in the frontier of world biology after five yearsefforts. The worlds first cloned somatic monkey Zhongzhong was born on November 27, 2017. Ten days later, the second cloned monkey Huahua was born.

With this technology, a large number of model monkeys with the same genetic background and gene editing can be bred by the scientific research team in the next year.

Yang Hui told China Economic Weekly that with a cloned monkey model, it would be easier to edit genes. If you think of the pathogenic genes, you can edit the somatic cells in vitro and clone them to complete the transplantation. This is a disease model. We do a series of experiments on monkeys to understand how the disease came about and then use interventions to treat it.

Tuyere Industry: Gene Detection

Precise Guidance Weapon for Locating Cancer Gene Mutation

Nowadays, gene detection has become one of the most promising technologies in the field of biological science. For patients, unlike in the past era of radiotherapy and chemotherapy, precise medical treatment should first understand the types of tumors and the mutations of pathogenic genes before targeting therapy according to the mutated genes.

According to BBCResearchs forecast, the global gene sequencing market will reach 11.7 billion US dollars in 2018, and the compound growth rate is expected to reach 21% in the next four years. Data from the China Business Industry Research Institute also show that the global precision medical market will grow at an annual rate of 15% from 2016 to 2020. The global precision medical market is expected to reach 105 billion US dollars by 2020.

At present, there are more than 500 enterprises involved in gene testing in China.

Wuning, the executive vice-chairman of the Biomedical Industrialization Working Committee of the Chinese High-tech Industrialization Research Association and the head of the drafting group of the Autonomous Standards for the Quality Control of Immunocyte Preparations of the Chinese Medical Biotechnology Association, told China Economic Weekly that there are more and more drugs available for targeted treatment of tumors, but targeted and cancer are needed. Gene mutation in cells is the target. Targeted drugs are like precision guided missiles. But in order to carry out the mission of missiles, the first thing is to lock the target. Gene detection is the weapon to lock the target.

For example, in lung cancer, the most common mutation in non-small cell lung cancer is EGFR (epidermal growth factor receptor). The specific EGFR inhibitor, such as Iressa, can be selected only after the mutation is identified. If the ALK gene mutation, the appropriate target drug is clozotinib, if used Iressa, may be completely ineffective.

However, Chen Haiquan, Director of Thoracic Surgery and Director of Lung Cancer Prevention and Treatment Center of Tumor Hospital Affiliated to Fudan University, told China Economic Weekly that gene mutation can not be used as a therapeutic target. For example, KARS mutation is clearly known to be the root cause of gene mutation, but still no targeted therapy has been found.

China emphasizes downstream applications while the upstream is weak.

Li Nan, Director of Bioinformatics Big Data Department of Hangzhou Ruip Gene Technology Co., Ltd., told China Economic Weekly that at present, Europe and the United States are leading the development direction of the global industry in gene detection industry chain. Upstream gene detection solutions providers such as Illumina and ThermoFisher have nearly monopolized the global market; downstream detection service providers are located in the world. Relatively mature service models have been established in various application areas, such as Foundation Medicine, Guardant Health and so on.

Gene testing in developed countries in Europe and the United States has a fairly high prevalence. FDA (Food and Drug Administration) has mandated EGFR, KRAS and other gene detection before clinical use of targeted drugs. Another authority, NCCN (American Cancer Comprehensive Therapy Network), has also incorporated EGFR, ERCC1 and other gene tests into cancer treatment guidelines. Li Nan said that other countries and regions in the world are at the stage of development in the field of gene testing, using technology from the United States.

He told China Economic Weekly that because Chinas genetic testing market started late, although the country attaches great importance to the development of precision medicine, there are still many challenges.

In his view, China has made good achievements in the field of gene detection, especially in the frontier technology research and development of clinical applications and product development, and has gradually stepped out of its own world. However, efforts are still needed in sequencing platform technology and upstream product development.

On December 5, Wang Zhimin, a representative of the Shanghai Peoples Congress and director of the research and Planning Department of the Shanghai Human Genome Research Center (the Southern Research Center of the National Human Genome), said that under the background of increasing trade frictions in the world, the import and export of biopharmaceuticals, including life science research and gene sequencing, might be affected. To be quite frank, our countrys high-end sequencer has not really realized the localization, almost all rely on American instruments and equipment. In addition to the equipment, the material behind is also a large piece.

More importantly, if you know the upstream of the gene sequencing industry, you can get a general understanding of research and development in the gene field in other countries and regions, said Wang Zhimin. For example, probes designed for research and development in the field of genetics are now mainly imported from the United States. If we want to develop original drugs for a disease, as soon as the project has just started, and the project has not progressed much, the other side can analyze the general direction and extent of research progress through the types of probes we want to order and the areas where the probes are concentrated.

Especially in the era of big data, before we do any disease research, we have to go to NCBI (National Biotechnology Information Center, Medical Gene Database) to look up information. Others can learn what you are interested in according to the heat of your search. Wang Zhimin said.

Having been called to a halt, ready to go after the lifting of the ban

The reporter of China Economic Weekly noticed that the former State Administration of Food and Drug Administration and the State Health Planning Commission jointly issued a notice on February 9, 2014 that no medical institution should carry out clinical application of gene sequencing until the relevant access standards and management norms were promulgated. NIPT (non-invasive DNA prenatal testing) is the most affected.

At that time, the relevant person in charge of the former State Administration of Food and Drug Supervision explained that the use of clinical sequencing technology was faced with many standard deficiencies, technology, price, quality supervision, ethical privacy protection and other issues need to be standardized, so the regulatory authorities hope to regulate the industry through temporary suspension.

Wang Caiyue, Senior Product Manager of Zhongan Life, told China Economic Weekly that no standard is one of the main obstacles to the rapid development of gene testing industry. If the technicians of the two companies search the scientific literature to select gene loci for gene detection, there is no uniform standard for evaluation methods and databases, and the final detection results sometimes vary greatly. The call was at the medical end. During the suspension period, the state began to promulgate relevant policies and standards, and the whole industry began to develop in 2015.

In early 2015, the former State Health Planning Commission issued the Notice on the Pilot Work of Prenatal Screening and Clinical Application of High-throughput Gene Sequencing in Prenatal Diagnostic Institutions and the Notice on the Pilot Work of Clinical Application of High-throughput Gene Sequencing Technology. 109 medical institutions and many testing institutions in Beiguang and Shenzhen were included in the pilot units, which were interpreted as clinical genetic testing by the industry. The application is called off for one year before the switch is opened.

After the relevant policies and standards standardized genetic testing, a series of incentive policies emerged one after another.

Rip Genes Li Nan believes that government-led research investment can promote the transformation of medical model to precision, and will comprehensively promote the progress of disease prevention, diagnosis, treatment and prognosis-related research and drug development.

The industry calls for genetic testing to be included in health insurance

Wuning, the standing vice-chairman of the working committee of biomedical industrialization of China High-tech Industrialization Research Association and the chairman of the drafting group of Self-Discipline Standards for the Quality Control of Immunocyte Preparations of China Medical Biotechnology Association, introduced to the reporter of China Economic Weekly that in recent years, the cancer gene detection service in China has shown a rapid development trend, and the first-and second-tier urban hospitals have gradually developed. Cancer genetic testing projects have been popularized, and a number of institutions have emerged to introduce advanced technology and provide genetic testing services. In some areas of China, gene testing has also been included in the scope of medical insurance.

But after all, there are a few who are included in health insurance.

Many provinces and municipalities in the country have included targeted drugs for cancer treatment into the payment scope of special drugs for major disease insurance. However, before opening, hospitals need to confirm whether the targeted drugs correspond to the gene mutation of patients, and need genetic testing. However, in many areas, gene testing is not included in medical insurance, which leads to some patients who are economically difficult to pay for gene testing, and can not directly purchase targeted drugs included in medical insurance.

It is reported that the detection rate of genes in Beijing, Shanghai and Guangzhou is only 40%-50%, and that in second-and third-tier cities is lower, only 20%-30%. The low detection rate is due to the high cost of detection, especially after targeting drugs are included in medical insurance, a considerable number of patients chooseblind eating, which not only delays the treatment, but also affects the therapeutic effect. Wuning said.

Targeted therapy for lung cancer, for example, costs tens of thousands to tens of thousands of yuan to perform gene testing to determine which gene mutation is. Gene testing companies at different levels are quite different from each other in terms of testing equipment, data analysis, expert team, clinical matching and so on.

In fact, the price of genetic testing is on the downward trend, which has dropped from about $10,000 to about $1,000. Wang Caiyue told China Economic Weekly that genetic testing is very detailed in medical insurance. For example, NIPT has been insured in many provinces, and the detection of tumor sites in Zhejiang and Jiangsu has also been insured. However, there are 3 billion bases in humans, and only two or three sites with a clear relationship with disease have entered health insurance.

Industry insiders believe that the integration of genetic testing into medical insurance is a major international trend, and it is very possible that genetic diagnosis will be integrated into medical insurance nationwide in the future.

The world will enter the blowout period of gene therapy drugs

Vitrakvi is not available to 99% of patients with solid tumors.

Recently, news such as anti-cancer magic drug, cancer cure rate can reach 75% and its not far for human beings to conquer cancer spread widely on the Internet. Vitrakvi, a new anti-cancer drug, has aroused public concern.

Previously, media reports reported that Vitrakvi, a broad-spectrum anticancer drug officially approved by the US FDA, could treat up to 17 types of cancer, with a cure rate of up to 75%. After the news sparked a heated debate, Bayer, Vitrakvis research and development company, clarified that the cure rate of the drug was as high as 75% untrue and the remission rate was 75%.

Wang Tao, director of Ripps Digital Health Department, told China Economic Weekly that Vitrakvi is a cross-cancer drug targeting specific targets. Regardless of the type of cancer (tissue/cell/site), Vitrakvi can be used as long as NTRK fusion gene is present.

Like other targeted drugs, long-term inhibition of NTRK can also lead to drug resistance, requiring the development of second-generation or even third-generation drugs targeting mutant targets. In addition, although NTRK mutations exist in some rare tumors, NTRK mutations are relatively low in some common tumors, such as lung cancer. Li Chao, a senior R&D officer from a multinational pharmaceutical factory and a doctor of chemistry from Peking University, said.

According to industry analysis, NTRK gene mutation is less than 1% in most solid tumour types, that is to say, 99% of solid tumour patients do not use this drug at present.

Vitrakvi is not the first drug to be effective for multiple tumors, Fang said. Keytruda, a MD-1 inhibitor of Mosadong, which was launched last year, is also effective for multiple tumors. But K is a monoclonal antibody drug, while Vitrakvi is a small molecule compound.

Prices of Gene Therapeutic Drugs or Their Significant Decline

The good news is that cancer-targeting drugs have developed rapidly in recent years.

The global cancer drug market will exceed $150 billion in 2020, up nearly 50% from $113 billion in 2016, according to a report by IMS Health, a pharmaceutical health market research company.

Targeted biological drugs, as one of the main cancer drugs in the future, account for nearly 50% of the global sales of cancer drugs in 2016. In 2016, 631 follow-up cancer drug research projects were in clinical phase II/III, of which nearly 90% were targeted drugs.

For example, Lin Rui, director of R&D of Ripp Gene Technology, said that EGFR mutations are more common in lung cancer patients in China. Ektinib, developed by Beida Pharmaceutical, is specifically targeted at EGFR mutations. It is not only the first small molecule targeted anticancer drug with independent intellectual property rights in China, but also greatly reduces the treatment costs of patients.

At present, many domestic innovative pharmaceutical companies are rushing to develop a new generation of targeted imported drugs for T790M mutation. Ivetini of Eisen Pharmaceutical is in the stage of new drug declaration.

Yang Hui, a researcher at the Institute of Neuroscience of the Chinese Academy of Sciences, told China Economic Weekly that there will be dozens and hundreds of gene therapy drugs in the next four years worldwide, and hundreds and thousands of drugs will emerge in the next 10 years.

The next era will be the era of blowout of gene therapy drugs. Yang Hui said.

With the widespread use of gene therapy drugs, the current price of injections is hundreds of thousands of dollars, which is expected to drop to tens of thousands of dollars.

Right and wrong of gene editing

Gene editing can treat hereditary diseases

On December 3, a US genetic editing company announced that it would launch a clinical trial using CRISPR gene editing technology to treat a hereditary eye disease. The application has been accepted by US regulatory authorities.

In this clinical trial, the target of gene editing is the photoreceptor cells in the eyes of patients with congenital amaurosis. This is a somatic cell, not a germ cell, whose genetic information will not be passed on to the next generation, so it does not involve ethical issues.

It is expected to become the first therapy in the world to use CRISPR technology in human body.

The reporter of China Economic Weekly learned that the Shanghai Academy of Life Sciences of the Chinese Academy of Sciences had already started similar research experiments. Yang Hui, a researcher at the Institute of Neuroscience, Chinese Academy of Sciences, said that there are more than 7,000 rare diseases in China, 80% of which are monogenic hereditary diseases, and all of them have the possibility of treatment. The same thing we do with scientists in the United States is how to cure these rare sick children after they are born.

It is reported that gene editing technology is mainly to modify our genetic material DNA, including deletion, insertion, replacement and other ways, in essence, is to make gene drugs.

Yang Hui told China Economic Weekly that blindness and congenital deafness are mostly caused by single-gene hereditary diseases. If a child is intervened at birth and corrected by gene editing, the child will be as normal after birth.

Yang Hui, a researcher at the Institute of Neuroscience, Chinese Academy of Sciences, is doing genetic research.

Error in Gene Editing or Extinction of Human Beings

Wuning, the standing vice-chairman of the working committee of biomedical industrialization of the Chinese Association of High-tech Industrialization and the chairman of the drafting group of Self-Discipline Standards for the Quality Control of Immunocyte Preparations of the Chinese Medical Biotechnology Association, believes that CRISPR has many potential benefits, but it also has limitations. Unexpected effects and all unknown variables are the drawbacks of this new technology, and new ethical issues and controversies have emerged recently as a result of human trials.

As for gene editing, Chen Haiquan, director of thoracic surgery and director of lung cancer prevention and treatment center of Tumor Hospital Affiliated to Fudan University, told China Economic Weekly, The advantage of gene editing is that it can modify DNA, become a research tool, or optimize DNA to make the genes coded have better performance. The disadvantage is that human understanding of DNA information is not thorough enough, so the so-called optimization process does not necessarily produce better DNA.

Chen Haiquan emphasized that the process of gene editing has a certain failure rate, once the consequences of failure are unknown, it may cause very serious consequences. In practice, the industry allows systematic gene editing, that is, post-natal genetic changes are permitted, and embryo genetic editing is generally recognized as not permitted by the industry.

An insider told China Economic Weekly that some people are innately immune to some diseases because of certain segments of the gene. If these fragments are found and reproduced accurately, then humans can be immune to these diseases. Conversely, mistakes in gene editing may lead to serious genetic or infectious diseases in otherwise healthy humans. For example, when an editor fails, the editor may have obvious physical defects and inherit them. Or there may be a serious disease leading to the death of life. If the disease is transmitted, even through the air, the consequences will be very serious.

He cited the fact that influenza killed more than 400,000 French people during World War II, when there was no targeted treatment, and that if a highly contagious flu was caused by a mistake in gene editing at that time, it could lead to massive human infection or even death. In other words, in the process of gene editing, genes that cannot bear or die prematurely are inadvertently present, and if they are highly infectious, humans may soon become extinct.

NPC deputies appeal for legislation to protect genetic information security

The development of gene technology has also brought about the problem of gene information security.

Yang Hui, a researcher at the Institute of Neuroscience of the Chinese Academy of Sciences, worries that, with the continuous understanding of gene sequences, predictions in gene testing will become more accurate, which may lead to invisible discrimination, For example, if I have a certain risk of disease, will I be eliminated from the job market? Do I have to pay twice as much for insurance as others? Are insurance companies looking for people who are not susceptible to disease to insure?

China Insurance Regulatory Commission (CIRC) published on its official website on November 15, 2017 Health Insurance Management Measures (Draft for Consulting Opinions) that is clear, insurance companies should not ask for customers genetic testing data, nor can it be used as the basis for verification and fee transfer.

In addition to regulation at the insurance level, genetic safety in scientific research has also been included in the regulatory sequence.

On October 24, 2018, the Ministry of Science and Technology published information on administrative penalties for human genetic resources on its official website for the first time, involving six companies. Among them, Huashan Hospital and Huada Gene carried out international cooperation research on human genetic resources in China with Oxford University without permission, and transferred some information of human genetic resources from the Internet, which violated the Interim Measures for the Management of Human Genetic Resources and attracted the attention of netizens.

On October 26, Shenzhen Huada Gene Science and Technology Co., Ltd. issued a clarification statement, saying that the study was completed in China. Samples and data were all kept in Shenzhen National Gene Bank, and there was no exit of any genetic resources data. The foreign authors in the study have not participated in any analysis work that touches on the original data, mainly contributing to the intelligence of scientific research ideas and algorithm design.

Wang Zhimin, deputy of the Shanghai Peoples Congress and director of the research and Planning Department of the Shanghai Human Genome Research Center, believes that ethical norms play a very important role in the first class of medical studentsenrollment in the context of the increasingly rapid development of interdisciplinary disciplines.

He also said: Now the technology of gene sequencing is more and more developed, the cost is lower and lower, and it will be more convenient to obtain personal genetic information in the future. The protection of genetic privacy is a major and long-term problem, and we should study how to do it from the perspective of legislation. Because the genetic information that belongs to each of us is likely to be trafficked and used by others in the future.

Source: Gu Ying_N6577, Responsible Editor of China Economic Weekly